Regulation of functions of drug transporters in renal tubules by inflammatory cytokines and implication of its significance

在内毒素(LPS)诱导的炎性大鼠模型中，甲氨蝶呤(MTX)的血浆清除率下降了约50%。提示肾小球滤过和肾小管分泌参与了内毒素引起的MTX肾清除量下降。肾组织/血浆浓度比和肾组织到肾小管腔的清除率也降低，与肾组织有机阴离子转运体(rOAT1、rOAT3、rMRP2、rMRP4)表达水平降低相当。综上所述，在内毒素处理的大鼠中，MTX的肾清除量显著降低，提示肾小球滤过率降低以及肾小管有机阴离子转运体表达水平降低是其作用机制之一。

Plasma clearance of methotrexate (MTX) decreased about 50% in the inflammatory rat model, which is prepared by the administration of lipopolysaccharide (LPS). Involvement of glomerular filtration as well as tubular secretion were suggested in the decreased renal clearance of MTX by LPS. Renal tissue/plasma concentration ratio and efflux clearance from renal tissue to the tubular lumen also decreased in LPS rats, and were comparable to the decreased expression levels of organic anion transporters (rOAT1, rOAT3, rMRP2, rMRP4) in the kidney. In conclusion, the renal clearance of MTX markedly decreased in the LPS-treated rats and the contribution of decreased glomerular filtration as well as decreased expression levels of organic anion transporters in the renal tubules were suggested.